ABSTRACT
First marketed in Japan in the 1990s, olprinone is a newly developed phosphodiesterase Ⅲ (PDE Ⅲ) inhibitor. It can not only increase cardiac contractility and also reduce peripheral vascular resistance without affecting mean arterial pressure and heart rate. At present, olprinone is mainly used in the treatment of acute heart failure and postoperative acute cardiac insufficiency. Through selectively inhibiting the activity of PDEⅢ and increasing the concentration of cyclic adenosine monophosphate (cAMP) by blocking its degradation, olprinone accelerates the influx of Ca2+in cardiac myocytes, leading to enhancement of myocardial contractility; and on the other hand, decreases the influx of Ca2+in vascular smooth muscle cells, resulting in dilation of peripheral blood vessels. Recently, a considerable amount of research has been conducted on olprinone in terms of pulmonary hypertension, myocardial ischemia/reperfusion (I/R) injury, and arrhythmia. In this review, we summarize the application of olprinione in acute heart failure, pulmonary hypertension, myocardial I/R injury, and arrhythmia, and analyze its application value and related progress in cardiovascular diseases.
ABSTRACT
Objective To evaluate the efficacy and safety of oprinon hydrochloride in increasing cardiac pump function and stabilizing hemodynamics and preventing common complications after cardiac valve replacement. Methods Sixty-two patients were admitted to the First Affiliated Hospital of Zhengzhou University from January to August 2018 to undergo cardiac valve replacement operation, post-operatively, 32 patients using oprinon hydrochloride were in the observation group and 30 patients using milrinone were in the control group. Both groups received basic treatment, additionally the observation group was given oprinon hydrochloride intravenous pump injection for 48 hours and the control group was given milrinone intravenous pump injection for 48 hours. The changes of vital signs (blood pressure, heart rate, respiratory rate), cardiac function, hemodynamics, biochemical indexes, electrocardiogram, cardiac color Doppler ultrasound and adverse reactions were observed before and after treatment in the two groups. The incidence of cardiovascular events (worsening, re-hospitalization and death) was followed up 1 month after discharge. Results The left ventricular ejection fraction (LVEF), central venous pressure (CVP), arterial oxygen saturation (SaO2), arterial partial pressure of oxygen (PaO2), N-terminal B-type natriuria (NT-proBNP), lactic acid, serum creatinine (SCr), blood sodium and potassium of the two groups after treatment were not statistically significant compared with those before treatment [LVEF: the control group was 0.52±0.09 vs. 0.60±0.09, the observation group was 0.62±0.12 vs. 0.50±0.11;CVP (mmHg, 1 mmHg = 0.133 kPa): the control group was 11.2±2.8 vs. 13.0±2.9, the observation group was 13.0±2.5 vs. 10.5±3.6; SaO2: the control group was 0.98 (0.90, 0.99) vs. 0.99 (0.98, 1.00), the observation group was 0.95 (0.94, 0.98) vs. 0.96 (0.90, 1.00); PaO2(mmHg): the control group was 100.5 (63.8, 135.3) vs. 99.5 (82.3, 179.5), the observation group was 95.0 (85.5, 129.0) vs. 75.5 (59.0, 138.3); NT-proBNP (pg/L): the control group was 1.45 (1.34, 3.31) vs. 0.92 (0.42, 1.81), the observation group was 0.47 (0.35, 1.37) vs. 2.07 (1.27, 4.44); lactic acid (mmol/L): the control group was 3.6 (2.4, 4.5) vs. 1.4 (1.2, 3.1), the observation group was 1.3 (1.1, 2.1) vs. 3.1 (1.4, 3.7); SCr (μmol/L): the control group was 106.7±35.9 vs. 84.4±20.3, the observation group was 96.5±40.7 vs. 77.1±23.1; sodium (mmol/L):the control group was 141.4±7.2 vs. 143.6±4.2, the observation group was 142.9±3.6 vs. 140.5±4.5; potassium (mmol/L): the control group was 4.6±0.9 vs. 4.8±0.6, the observation group was 4.8±0.6 vs. 4.1±0.6, all P > 0.05];the comparisons between the following indicators in levels before and after treatment in the two groups had statistical significant differences: the peripheral arterial pressure (PAP), white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), alanine aminotransferas (ALT) and aspartate aminotransferase (AST) [PAP (mmHg): the control group was 33.0 (24.0, 59.3) vs. 38.0 (34.8, 46.0), the observation group was 30.0 (25.0, 32.0) vs. 53.5 (29.3, 66.5); WBC (×109/L):the control group was 12.2 (10.4, 13.9) vs. 5.7 (4.4, 8.6), the observation group was: 8.4 (3.7, 11.8) vs. 8.6 (5.7, 12.4); Hb (g/L): the control group was 95.6±12.9 vs. 130.3±15.0, the observation group was 111.1±22.6 vs. 112.4±24.6; PLT (×109/L): the control group was 95.2±21.3 vs. 168.7±32.6, the observation group was 146.3±68.1 vs. 132.7±45.1;ALT (U/L): the control group was 36.5 (15.3, 80.5) vs. 14.0 (11.0, 19.0), the observation group was 15.0 (10.0, 32.3) vs. 20.3 (12.0, 35.8); AST (U/L): the control group was 33.0 (20.0, 83.0) vs. 16.5 (16.7, 28.8), the observation group was 35.5 (12.3, 56.8) vs. 75.5 (45.3, 140.3), all P < 0.05]; after treatment, the urea nitrogen (BUN) level in control group was higher than that before treatment (mmol/L: 11.4±4.7 vs. 7.1±2.5), while BUN in the observation group was decreased (mmol/L: 6.5 ±3.3 vs. 9.1±3.8), there was statistical significant difference in BUN level between the two groups after treatment (P < 0.05). The levels of systolic blood pressure and respiratory rate after treatment in the two groups were significantly higher than those before treatment (all P < 0.05). After treatment, the diastolic blood pressure in the observation group was increased, but there was no significant difference in the control group before and after treatment, and the diastolic blood pressure in the observation group after treatment was higher than that in the control group (mmHg: 67.8±9.9 vs. 62.0±10.5, P < 0.05). According to the New York Heart Association Heart (NYHA) function efficacy assessment score, the total effective rate of the observation group was higher than that of the control group [93.7% (30/32) vs. 83.3% (25/30), P > 0.05]. There was no statistical significant difference in the incidence of adverse reactions between the observation group and the control group [12.5% (4/32) vs. 30.0% (9/30), P > 0.05]. The patients in the two groups were followed up for one month after discharge, 9 cases (30.0%) in the control group were re-hospitalized due to heart failure, and 3 cases (9.4%) in the observation group were re-hospitalized due to heart failure, there was no statistical significant difference between the two groups in re-hospitalization rate (P > 0.05). Conclusion Oprinone hydrochloride can effectively improve cardiac function and maintain hemodynamic stability of patients after heart valve replacement surgery.
ABSTRACT
Objective To observe the effects of olprinone on ischemia/reperfusion (I/R) induced myocardial injury in male (Sprague-Dawley, SD rats) and explore its mechanisms. Methods Rats were subjected to a 30-min coronary arterial occlusion followed by 24-hour reperfusion. The survival rats were randomly divided into sham group (n=6), ischemia reperfusion group (I/R group, n=9), ischemia reperfusion+low dose of olprinone group(IR+olprinone-L group, n=6), ischemia reperfusion+medium dose of olprinone group (IR+olprinone-M group, n=6),ischemia reperfusion +high dose of olprinone group (IR+olprinone-H group, n=6). A MAP heart function analysis system was used to measure hemodynamic parameters; TTC staining method was used to detect the myocardial infarct size;24-hour mortality of SD rats was recorded; western blot was used to detect the levels of Caspase-3, Bax,Bcl-2, LC3B/LC3A,Beclin-1. Results Cardiac function in I/R group was lower than that in sham group, which was significantly improved by pretreatment with olprinone (P＜0.01),but systolic arterial pressure (SAP) diastolic arterial pressure (DAP) mean arterial pressure (MAP) mean pressure developed in left ventricle (Pmean) had no significant difference (P＞0.05). The percentage of myocardial infarct size in olprinone-M and olprinone-H group was lower than that in I/R group (P＜0.05).There was no significant difference in mortality among groups within 24 hours. Compared with sham group, the expressions of Caspase-3 and Bax were obviously up-regulated in I/R group (P＜0.01), whereas caspase-3 was down-regulated in olprinone-M group (P＜0.05) and Bax was inhibited by different doses of olprinone (P＜0.05), but the expression of Bcl-2 increased (P＜0.05); furthermore, the ratio of Bcl-2/Bax decreased in I/R group (P＜0.01) and increased with different degrees in different doses of olprinone (P＜0.05). Meanwhile, compared with sham group, the expression of Beclin-1 was up-regulated in I/R group(P＜0.05),and also increased in olprinone-L and olprinone-M groups(P＜0.05), but the ratio of Bcl-2 /Beclin-1 decreased in different doses of olprinone making statistically significant difference only in olprinone-M group (P＜0.05). Moreover, different doses of olprinone elevated the different ratios of LC3B/LC3A (P＜0.05), and this elevated ratio in olprinone-M group at median among groups. Conclusions Olprinone can strengthen the cardiac function after myocardial ischemia/reperfusion injury, without leading to disorders in hemodynamics; by regulating autophagy with anti-apoptotic protein, olprinone can make autophagy to an appropriate level using the mechanism of autophagy to preventing the myocardium from injury.